1-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino]benzotriazole-5-carboxylic acid | 1227244-63-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 1-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino]benzotriazole-5-carboxylic acid
• 英文别名: 1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-1H-benzotriazole-5-carboxylic acid；CBt-PMN；1-(3,5,5,8,8-Pentamethyl-6,7-dihydronaphthalen-2-yl)benzotriazole-5-carboxylic acid；1-(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl)benzotriazole-5-carboxylic acid
• CAS: 1227244-63-4
• 化学式: C₂₂H₂₅N₃O₂
• 分子量: 363.459
• InChiKey: QSRQAKVNYDAVIT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  68
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino]benzotriazole-5-carboxylic acid 在 potassium fluoride 、 N-溴代丁二酰亚胺(NBS) 、 硫酸 、 potassium carbonate 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 水 、 乙腈 为溶剂， 反应 25.17h， 生成
  参考文献：
  名称：

  Fluorine-18 (18F)-labeled retinoid x receptor (RXR) partial agonist whose tissue transferability is affected by other RXR ligands

  摘要：

  Bexarotene (1), a retinoid X receptor (RXR) agonist approved for the treatment of cutaneous T cell lymphoma (CTCL), was reported to migrate into baboon brain based on findings obtained by positron emission tomography (PET) with a C-11-labeled tracer. However, co-administration of non-radioactive 1 had no effect on the distribution of [C-11]1, probably due to non-specific binding of 1 as a result of its high lipophilicity. Here, we report a fluorine-18 (F-18)-labeled PET tracer [F-18] 6 derived from RXR partial agonist CBt-PMN (2), which has lower lipophilicity and weaker RXR-binding ability than [C-11]1. The concomitant administration of 1 or 2 with [F-18]6 with resulted in decreased accumulation of [F-18]6 in liver, together with increased brain uptake and increased accumulation in kidney and muscle, as visualized by PET. A plausible explanation of these findings is the inhibition of [F-18]6 uptake into the liver by concomitantly administered 1 or 2, leading to an increase in blood concentration of [F-18]6 followed by increased accumulation in other tissues.

  DOI：

  10.1016/j.bmc.2019.05.045
• 作为产物：
  描述：

  4-碘苯甲酸 在 氯化亚砜 、 硫酸 、 palladium on activated charcoal 、 氢气 、 硝酸 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium hydroxide 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙酸乙酯 、 甲苯 为溶剂， 反应 7.75h， 生成 1-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino]benzotriazole-5-carboxylic acid
  参考文献：
  名称：

  RXR Partial Agonist CBt-PMN Exerts Therapeutic Effects on Type 2 Diabetes without the Side Effects of RXR Full Agonists

  摘要：

  Treating insulin resistance and type 2 diabetes in rodents, currently known retinoid X receptor (RXR) agonists induce significant adverse effects. Here we introduce a novel RXR partial agonist CBt-PMN (11b), which shows a potent glucose-lowering effect and improvements of insulin secretion and glucose tolerance without the serious adverse effects caused by RXR full agonists. We suggest that RXR partial agonists may be a new class of antitype 2 diabetes drug candidates.

  DOI：

  10.1021/ml300055n

文献信息

• [EN] THERAPEUTIC COMPOUNDS<br/>[FR] COMPOSÉS THÉRAPEUTIQUES
  申请人：UNIV ARIZONA STATE

  公开号：WO2015130973A1

  公开（公告）日：2015-09-03

  The invention provides compounds and compositions that are useful for treating conditions including Alzheimer's disease, Parkinson's disease, diabetes, cancer, and psychotic disorders such as schizophrenia.

  这项发明提供了用于治疗包括阿尔茨海默病、帕金森病、糖尿病、癌症以及精神分裂症等疾病的化合物和组合物。
• Therapeutic compounds
  申请人：ARIZONA BOARD OF REGENTS ON BEHALF OF ARIZONA STATE UNIVERSITY

  公开号：US10005741B2

  公开（公告）日：2018-06-26

  The invention provides compounds and compositions that are useful for treating conditions including Alzheimer's disease, Parkinson's disease, diabetes, cancer, and psychotic disorders such as schizophrenia.

  本发明提供了可用于治疗阿尔茨海默病、帕金森病、糖尿病、癌症和精神障碍（如精神分裂症）等疾病的化合物和组合物。
• Pharmaceutical composition for treatment or prevention of neurodegenerative diseases
  申请人：NATIONAL UNIVERSITY CORPORATION OKAYAMA UNIVERSITY

  公开号：US10285985B2

  公开（公告）日：2019-05-14

  There is provided a pharmaceutical composition for treatment or prevention of a neurodegenerative disease, comprising an RXR agonist as an active ingredient, which is a compound represented by formula (1) or (2). The pharmaceutical composition is effective in treatment or prevention of neurodegenerative diseases such as dementia, Parkinson's disease and multiple sclerosis with reducing side effects such as enlargement of the liver and elevation of blood triglyceride level. In these formulas, A represents CMe2, N-methyl, N-ethyl or N-isopropyl; X represents N, CH or C—CF3; Y and Z represent N or CH; R1 represents methyl, hydroxy, methoxy or ethoxy; R2 represents H, methyl or ethyl; B represents NR3 or CHR3; R3 represents alkyl; and R4 represents H, halogen, alkyl, alkenyl, aryl, alkynyl, alkoxy or acyl.

  本发明提供了一种用于治疗或预防神经退行性疾病的药物组合物，其活性成分包括一种 RXR 激动剂，它是由式（1）或（2）表示的化合物。该药物组合物能有效治疗或预防神经退行性疾病，如痴呆症、帕金森病和多发性硬化症，并能减少副作用，如肝脏肿大和血甘油三酯水平升高。在这些式子中，A 代表 CMe2、N-甲基、N-乙基或 N-异丙基；X 代表 N、CH 或 C-CF3；Y 和 Z 代表 N 或 CH；R1 代表甲基、羟基、甲氧基或乙氧基；R2 代表 H、甲基或乙基；B 代表 NR3 或 CHR3；R3 代表烷基；R4 代表 H、卤素、烷基、烯基、芳基、炔基、烷氧基或酰基。
• Medicinal composition for preventing or treating inflammatory respiratory disease
  申请人：NATIONAL UNIVERSITY CORPORATION OKAYAMA UNIVERSITY

  公开号：US11026932B2

  公开（公告）日：2021-06-08

  A method for treating an inflammatory respiratory disease, comprising administering an effective amount of an RXR agonist represented by formula (1) or (2) as an active ingredient. wherein D, R1, R2, X, Y, Z, R3, R4, X1, Y1, X2, Y2 and Z1 are defined.

  一种治疗炎症性呼吸道疾病的方法，包括施用有效量的式（1）或（2）代表的 RXR 激动剂作为活性成分。 其中定义了 D、R1、R2、X、Y、Z、R3、R4、X1、Y1、X2、Y2 和 Z1。
• THERAPEUTIC COMPOUNDS
  申请人：ARIZONA BOARD OF REGENTS ON BEHALF OF ARIZONA STATE UNIVERSITY

  公开号：US20170008859A1

  公开（公告）日：2017-01-12

  The invention provides compounds and compositions that are useful for treating conditions including Alzheimer's disease, Parkinson's disease, diabetes, cancer, and psychotic disorders such as schizophrenia.